Oncogenic Gαq activates RhoJ through PDZ-RhoGEF.

ABSTRACT: Oncogenic Gα_q causes uveal melanoma via non-canonical signaling pathways. This constitutively active mutant GTPase is also found in cutaneous melanoma, lung adenocarcinoma, and seminoma, as well as in benign vascular tumors, such as congenital hemangiomas. We recently described that PDZ-RhoGEF (also known as ARHGEF11), a canonical Gα_12/13 effector, is enabled by Gα_s Q227L to activate CdcIn addition, and we demonstrated that constitutively active Gα_q interacts with the PDZ-RhoGEF DH-PH catalytic module, but does not affect its binding to RhoA or Cdc. This suggests that it guides this RhoGEF to gain affinity for other GTPases. Since RhoJ, a small GTPase of the Cdc42 subfamily, has been involved in tumor-induced angiogenesis and the metastatic disse

SUBMITTER: Cervantes-Villagrana RD 

PROVIDER: S-EPMC10647656 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature